This research proposal investigates the neuroanatomy of sleep regulation over the 24-hour day. The suprachiasmatic nucleus (SCN) in the mammalian hypothalamus controls the timing of endogenous circadian rhythms such as sleep and wakefulness, but the mechanism(s) by which it exerts this temporal control is largely unknown. Neurons in the nearby ventrolateral preoptic area (VLPO) are active during sleep, and SCN neurons may directly stimulate VLPO neurons to facilitate sleep in the rat. To this end, the proposed experiments will characterize SCN neurons which synapse in the VLPO, and will establish the physiological significance of these connections. Specifically, the anatomical and neurochemical identity of SCN efferents to the VLPO will be examined by combining anterograde and retrograde tracer injections with immunohistochemical staining for neurotransmitters. The functional importance of SCN-VLPO connections will be demonstrated by physically interrupting this pathway and by pharmacological manipulations. The societal impact of sleep/circadian rhythms disorders is massive. An estimated 30-40 million Americans suffer from sleep disorders. With 20% of the American work force employed as shift-workers and with the pressures of a 24-hour society creating a nation of sleep-deprived workers, the timing of sleep becomes crucial to the health of America. Results of the proposed research could contribute importantly to the development of treatments and cures for the millions afflicted with sleep and circadian rhythms- related disorders, and the American public would substantially benefit from increased productivity and quality of life.